Three-dimensional experiments and individual based simulations show that cell proliferation drives melanoma nest formation in human skin tissue
Autor: | D. L. Sean McElwain, Alexander P Browning, Jacqui A. McGovern, Parvathi Haridas, Matthew J. Simpson |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Cell Survival Systems biology Human skin Biology Models Biological 03 medical and health sciences Individual based 0302 clinical medicine Nest Structural Biology Cell Movement medicine Melanoma nest Humans Colony Cell migration Melanoma cells Fibroblast Molecular Biology Melanoma lcsh:QH301-705.5 Cell proliferation 030304 developmental biology Skin 0303 health sciences Cell growth Applied Mathematics medicine.disease Computer Science Applications 3. Good health Cell biology Individual based model 030104 developmental biology medicine.anatomical_structure lcsh:Biology (General) Cluster Modeling and Simulation 030220 oncology & carcinogenesis 3D human skin model Keratinocyte Mathematical simulation Research Article Barrier assay |
Zdroj: | BMC Systems Biology, Vol 12, Iss 1, Pp 1-15 (2018) BMC Systems Biology |
ISSN: | 1752-0509 |
DOI: | 10.1186/s12918-018-0559-9 |
Popis: | BackgroundMelanoma can be diagnosed by identifying nests of cells on the skin surface. Understanding the processes that drive nest formation is important as these processes could be potential targets for new cancer drugs. Cell proliferation and cell migration are two potential mechanisms that could conceivably drive melanoma nest formation. However, it is unclear which one of these two putative mechanisms plays a dominant role in driving nest formation.ResultsWe use a suite of three-dimensional (3D) experiments in human skin tissue and a parallel series of 3D individual-based simulations to explore whether cell migration or cell proliferation plays a dominant role in nest formation. In the experiments we measure nest formation in populations of irradiated (non-proliferative) and non-irradiated (proliferative) melanoma cells, cultured together with primary keratinocyte and fibroblast cells on a 3D experimental human skin model. Results show that nest size depends on initial cell number and is driven primarily by cell proliferation rather than cell migration.ConclusionsWe find that nest size depends on initial cell number, and is driven primarily by cell proliferation rather than cell migration. All experimental results are consistent with simulation data from a 3D individual based model (IBM) of cell migration and cell proliferation. |
Databáze: | OpenAIRE |
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